Barbe F, Su J B, Guyene T T, Crozatier B, Ménard J, Hittinger L
Institut National de la santé et de la Recherche Médicale, Faculté de Médecine, Créteil, France.
Am J Physiol. 1996 Jun;270(6 Pt 2):H1985-92. doi: 10.1152/ajpheart.1996.270.6.H1985.
To determine the role of the renin-angiotensin system and the bradykinin pathway in the mechanism of action of angiotensin-converting enzyme inhibitors in heart failure, the acute effects of enalaprilat (1 mg/kg) were compared with those of a renin inhibitor (ciprokiren, 1 mg/kg i.v.) in 10 chronically instrumented conscious dogs with heart failure induced by right ventricular pacing (3 wk, 240 beats/min). The effects of enalaprilat and ciprokiren on bradykinin infusion (3, 10, and 30 micrograms/min) and the effects of enalaprilat in the presence of the bradykinin B2 receptor antagonist Hoe-140 (10 micrograms/kg i.v.) were also examined. Both inhibitors significantly decreased mean aortic pressure and increased cardiac output. However, enalaprilat induced significantly greater hemodynamic effects than ciprokiren (mean aortic pressure, -13 +/- 3 vs. -6 +/- 1 mmHg; cardiac output, 0.4 +/- 0.1 vs. 0.15 +/- 0.1 l/min). Bradykinin infusion led to dose-dependent decreases in mean aortic pressure and increases in cardiac output that were not modified by pretreatment with ciprokiren but were potentiated 10-fold by enalaprilat. Hoe-140 significantly reduced the hemodynamic effects of enalaprilat. Thus endogenous bradykinin is involved in the acute hemodynamic effects of enalaprilat in experimental heart failure.
为了确定肾素-血管紧张素系统和缓激肽途径在血管紧张素转换酶抑制剂治疗心力衰竭作用机制中的作用，在10只通过右心室起搏（3周，240次/分钟）诱导心力衰竭的慢性植入仪器的清醒犬中，比较了依那普利拉（1毫克/千克）与肾素抑制剂（西普罗瑞林，静脉注射1毫克/千克）的急性效应。还研究了依那普利拉和西普罗瑞林对缓激肽输注（3、10和30微克/分钟）的影响，以及在缓激肽B2受体拮抗剂Hoe-140（静脉注射10微克/千克）存在下依那普利拉的效应。两种抑制剂均显著降低平均主动脉压并增加心输出量。然而，依那普利拉诱导的血流动力学效应明显大于西普罗瑞林（平均主动脉压，-13±3对-6±1毫米汞柱；心输出量，0.4±0.1对0.15±0.1升/分钟）。缓激肽输注导致平均主动脉压呈剂量依赖性降低和心输出量增加，西普罗瑞林预处理对此无影响，但依那普利拉可使其增强10倍。Hoe-140显著降低了依那普利拉的血流动力学效应。因此，内源性缓激肽参与了依那普利拉在实验性心力衰竭中的急性血流动力学效应。
